The broad objective is to understand the relationship between cellular metabolism and (a) membrane ioni permeabilities, (b) transmembrane ionic gradients and (c) subcellular compartmentation of various ions. Mitochondral transport of Na ion ions via neutral exchange with protons will be stressed and the influence of this exchange upon mitochondrial pH gradients and distribution of anionic metabolites between mitochondrial and cytoplasmic compartments. The possible interplay between mitochondrial Ca plus 2 and Na ion transport will be studied to determine whether the translocation of Na ion may regulate the levels of Ca plus 2 within the cytosol. The experimetal approach will involve comparative studies of isolated cells, mitochondria and sub-mitochondrial particles to detail selected permeabilities and regulatory influences that may operate in vivo. Intact cell studies will involve alteration of intracellular ion levels together with specific alterations in the permeability of membranes with monovalent and divalent cation specific "ionophores", that is antibiotics capable of functioning as mobile ion "carriers". These agents will be employed also with mitochondria and submitochondrial particles in order to assess certain mchanistic details of cation transport (particularly Na ion and Ca plus 2. The influence of certain hormones upon plasma membrane permeability (e.g. glucagon, epinephrine, parathyroid hormone) and metabolism will form part of the above studies to examine the degree to which intracellular ions (especially calcium) determine the cellular resposne to these agents. The studies outlined will be applied princpally to isolated liver cells and corresponding subcellular components in comparison to a selected variety of tumor cells to determine the extent to which the indicated ions and their translocation between compartments affects especially the oxidative and glycolytic metabolism of tumor cells as well as relevant hormonal influences upon these processes in normal and noplastic cells.